Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy

J B Pain; M P Lê; M Caseris; C Amiel; L Lassel; C Charpentier; A Desnoyer; C Farnoux; G Pialoux; D Descamps; G Peytavin

doi:10.1128/AAC.00173-15

Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy

Antimicrob Agents Chemother. 2015;59(6):3660-2. doi: 10.1128/AAC.00173-15. Epub 2015 Apr 6.

Authors

J B Pain¹, M P Lê², M Caseris³, C Amiel⁴, L Lassel⁵, C Charpentier⁶, A Desnoyer¹, C Farnoux⁷, G Pialoux⁸, D Descamps⁶, G Peytavin⁹

Affiliations

¹ AP-HP, Clinical Pharmacology Department, Bichat Hospital, Paris, France.
² AP-HP, Clinical Pharmacology Department, Bichat Hospital, Paris, France minh.le@bch.aphp.fr.
³ AP-HP, General Pediatrics, Robert Debré Hospital, Paris, France.
⁴ AP-HP, Virology Department, Tenon Hospital, Paris, France AP-HP, UPMC Université Paris 06, UMRS CR7, Inserm U1135, Paris, France.
⁵ AP-HP, Infectious Diseases Unit, Tenon Hospital, Paris, France.
⁶ AP-HP, Virology Department, Bichat Hospital, Paris, France IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and UMR 1137, INSERM, Paris, France.
⁷ AP-HP, Neonatology Department, Robert Debré Hospital, Paris, France.
⁸ AP-HP, UPMC Université Paris 06, UMRS CR7, Inserm U1135, Paris, France.
⁹ AP-HP, Clinical Pharmacology Department, Bichat Hospital, Paris, France IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and UMR 1137, INSERM, Paris, France.

Abstract

We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate after maternal intensification of an antiretroviral (ARV) regimen by adding DTG. During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine, atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter inhibition and considering the infant's probable enzymatic immaturity, the DTG elimination half-life was estimated to be 4-fold longer in neonates than in adults.

MeSH terms

Adult
Anti-HIV Agents / pharmacokinetics*
Anti-HIV Agents / therapeutic use*
Atazanavir Sulfate / pharmacokinetics
Atazanavir Sulfate / therapeutic use
Cytochrome P-450 CYP3A / metabolism
Emtricitabine / pharmacokinetics
Emtricitabine / therapeutic use
Female
Glucuronosyltransferase / metabolism
HIV Infections / drug therapy
HIV Infections / metabolism
Heterocyclic Compounds, 3-Ring / pharmacokinetics*
Heterocyclic Compounds, 3-Ring / therapeutic use*
Humans
Infant, Newborn
Male
Oxazines
Piperazines
Pregnancy
Pyridones
Ritonavir / pharmacokinetics
Ritonavir / therapeutic use
Tenofovir / pharmacokinetics
Tenofovir / therapeutic use

Substances

Anti-HIV Agents
Heterocyclic Compounds, 3-Ring
Oxazines
Piperazines
Pyridones
Atazanavir Sulfate
Tenofovir
dolutegravir
Cytochrome P-450 CYP3A
UGT1A1 enzyme
Glucuronosyltransferase
Emtricitabine
Ritonavir